Type: Mutant inbred rat
Colour and related genotype: albino rat - a/a, Tyrc/Tyrc, h/h MHC: RT1u (Stephenson et al., 1985), contradiction: RT1w (Hashim et al., 1991)
Origin: Institut Pasteur (Lille, France) - 2008
Breeding: Difficult to rear, mating scheme: homozygous ♂ x heterozygous ♀
Description of our model
In 1970, Bazin and Beckers started breeding LOU rats from a possible Wistar colony origin kept at the University of Louvain in Belgium. From 28 parallel sub-lines LOU/C was selected for its high incidence of plasmacytomas and LOU/M for its low incidence of plasmacytomas.
In 1953, rats with the nude phenotype first appeared in an outbred hooded rat colony at the Rowett Research Institute in Aberdeen, Scotland.
No steps were undertaken to maintain the mutation. Because the phenotype reappeared in the 1970s in the same outbred colony (May et al., 1977; Festing et al., 1978), researchers concluded that the mutation was retained within the colony at a rather low allele frequency.
The autosomal recessive mutation is written rnu for rowett nude. The Institut Pasteur Lille (IPL) acquired it with the collaboration of M. Capron with M. BAZIN (1977). In 1993, the IPL decided to transfer the Nu mutation to a Lou/M rat background by successive back crosses.
This spontaneous rnu mutation is an autosomal recessive one and arises in the Foxn1 (forkhead box N1) gene (chromosome 10). It encodes for the transcription factor Foxn1 (also called Whn, winged-helix-nude). It regulates the expression of the keratin gene and the growth and differentiation of T cells .
The rnu mutation is associated with hairlessness and thymic aplasia:
- Phenotypically hairless (sparse hair growth possible), the Foxn1rnu/Foxn1rnu rat usually shows some short and thin hairs. Hair follicles are normal at birth, but keratinization, which normally occurs in the middle third of the follicle, is faulty and the hairs do not erupt. Epidermal keratinization is also faulty.
- Immunologically, the main feature of the nude mutation is congenital aplasia of the thymus, which is only present in a rudimentary form without any lymphocyte population (Fossum et al., 1980; Vos et al., 1980). There is no T cells but B cells remain functional.